Role of NADPH enzymes in pancreatic cancer.

Pancreas repair following injury involves reversible acinar-to-ductal metaplasia (ADM) and oncogenic KRAS mutations can progress ADM to pancreatic intraepithelial neoplasia (PanIN) and pancreatic ductal adenocarcinoma (PDAC) but, the metabolic alterations in these precancerous lesions are not established.

In 2 studies published in Nature Metabolism, researchers demonstrate decline in NADPH producing enzymes that reduce oxidative stress and protect the pancreatic cells.

In one study, the authors show aldehyde dehydrogenase 1 family member L2 (ALDH1L2), an NADPH-producing mitochondrial enzyme expression level decreases progressively during ADM and is completely absent in pancreatic ductal cells. ALDH1L2 loss elevates ROS and promotes ADM in a model of pancreatitis and accelerates tumor progression in models of pancreatic cancer.

In the 2nd study, the authors show NRF2-target genes are significantly induced in ADM. Among these, genes encoding NADPH-producing enzymes glucose-6-phosphate dehydrogenase (G6PD) and malic enzyme 1 (ME1), which participate in the regulation of oxidative stress.

In mouse models of pancreatic tumorigenesis, G6PD deficiency or Me1 loss increases reactive oxygen species and lipid peroxidation, which is accompanied by accelerated formation of ADM and PanIN lesions. The authors also show that Me1 loss, but not G6PD deficiency, promotes faster PDAC progression. sciencenewshighlights Science Mission https://www.nature.com/articles/s42255-026-01496-x https://sciencemission.com/NADPH-producing-enzymes https://sciencemission.com/ALDH1L2-regulates-reactive-oxygen-species

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New technology enables the insertion of a large segment of DNA into a genome, potentially expanding gene therapy treatment from cancellation of disease-causing mutations to replacement of an entire gene, scientists say.

Reporting in Nature, the researchers describe building upon a technique called prime editing by inserting DNA that attaches to the genome through a series of overlapping flaps. This method, which they call a prime assembly approach, avoids a bottleneck in the gene therapy field—a double-strand break to the donor DNA that can cause toxicity and kill cells.

“Using this method, we are doing genome assembly rather than making a small edit in a gene,” said Bin Liu, a co-lead author of the study and assistant professor of biological chemistry and pharmacology at The Ohio State University College of Medicine. “If we think of the genome as a book, we can remove one paragraph and replace it with a new one—or even rewrite a chapter.”

Scientists have uncovered an unexpected way cells can generate cancer-driving proteins—by cutting RNA into shorter, functional fragments rather than following the standard blueprint. This process, newly termed as “RNA dicing,” enables the production of a truncated form of the JAK1 protein that remains highly active and can promote tumor growth, particularly when normal gene function is disrupted.

The finding challenges conventional views of how genetic information is translated and points to a previously unrecognized mechanism that could influence cancer progression and response to targeted therapies.

The process by which cells turn genes into proteins has long been understood as precise and tightly controlled. But new research shows that cells can unexpectedly cut RNA into shorter fragments that still produce functional proteins, sometimes with harmful consequences.